Effects of food and calcium carbonate on the pharmacokinetics of lusutrombopag, a novel thrombopoietin receptor agonist.

This report describes 3 studies aimed at assessing the effects of food and calcium carbonate on the pharmacokinetic parameters of lusutrombopag in healthy subjects. METHODS: Three single-dose, open-label crossover studies were conducted. In study 1, eighteen healthy subjects were administered a single 2-mg dose of lusutrombopag as a single tablet in the fasted or fed state or as a 2-mg solution in the fasted state. In study 2, fifteen healthy subjects were administered a single 0.75-mg dose of lusutrombopag as three 0.25-mg tablets in the fasted or fed state, or in the fasted state with coadministration of 4000-mg calcium carbonate. In study 3, fifteen healthy subjects were administered 4-mg lusutrombopag as a single tablet in the fasted or fed state. Pharmacokinetic parameters were estimated from plasma lusutrombopag concentrations. FINDINGS: Mean fed versus fasted state ratios (90% CIs) of Cmax and AUC0-∞, respectively, were: 0.904 (0.864-0.945) and 0.920 (0.886-0.956) (study 1); 0.972 (0.864-1.09) and 1.02 (0.945-1.11) (study 2); and 0.917 (0.842-0.999) and 0.908 (0.855-0.964) (study 3). The respective ratios for calcium carbonate versus no calcium carbonate (fasted state) were 1.08 (0.959-1.21) and 0.989 (0.913-1.07) (study 2). Lusutrombopag exposure remained unaffected, except for a slight decrease in exposure with food. Lusutrombopag exposure did not change with the coadministration of calcium carbonate. These findings suggest that there was no clinica...
Source: Clinical Therapeutics - Category: Drugs & Pharmacology Authors: Tags: Clin Ther Source Type: research